Melamine is an organic base and a trimer of cyanamide, with a 1,3,5-triazine skeleton. Like cyanamide, it contains 66% nitrogen by mass and if mixed with resins, has fire retardant properties due to its release of nitrogen gas when burned or charred, and has several other industrial uses. Melamine is also a metabolite of cyromazine which is a pesticide. It is formed in the body of mammals that have ingested cyromazine. It has been reported that cyromazine can also be converted to melamine in plants.

Melamine combines with cyanuric acid in a ratio of 1:1 to form melamine cyanurate. It is also known as melamine-cyanuric acid adduct or melamine-cyanuric acid complex. Melamine cyanurate forms spoke-like crystals from aqueous solutions and has been implicated as a causative agent for toxicity seen in the Chinese protein export contaminations and the 2007 pet food recall. Melamine cyanurate is commonly used as a fire retardant.

Melamin is a German word coined by combining the names of two chemical products: Melam (a distillation derivative of ammonium thiocyanate) and Amin.

China is the world’s largest exporter of melamine, while its domestic consumption still grows by 10% per year. Surplus melamine has been a popular adulterant for feedstock and baby formula in mainland China for several years as it can make diluted or poor quality materials appear to be higher in protein content by elevating the total nitrogen content detected by some simple protein tests.

Melamine is often combined with formaldehyde to produce melamine resin, a synthetic polymer which is fire resistant and heat tolerant and melamine foam, a polymeric cleaning product. Melamine resin is a very versatile material with a highly stable structure. Uses for melamine include whiteboards (dry erase boards), floor tiles, glues, kitchenware, countertops, fire retardant fabrics, and commercial filters. Melamine is one of the major components in Pigment Yellow 150, a colorant in inks and plastics. Melamine can be easily molded while warm, but will set into a fixed form. This property makes it ideally suited to certain industrial applications.

Melamine by itself is nontoxic in low doses, but when combined with cyanuric acid it can cause fatal kidney stones due to the formation of an insoluble melamine cyanurate. Melamine is described as harmful if swallowed, inhaled or absorbed through the skin. Melamine is not metabolised and is rapidly eliminated in the urine with a half life in plasma of around 3 hours. Chronic exposure may cause cancer and reproductive problems. It also causes eye, skin and respiratory irritation. However, the toxic dose is on a par with common table salt with an LD50 of more than 3 grams per kilogram of bodyweight. US Food and Drug Administration (FDA) scientists have explained that when melamine and cyanuric acid are absorbed into the bloodstream., they concentrate and interact in the urine-filled renal microtubules, then crystallize and form large numbers of round, yellow crystals, which in turn block and damage the renal cells that line the tubes, causing the kidneys to malfunction.

No human data could be found on the oral toxicity of melamine. Data is available from animal feeding studies carried out in rats, mice and dogs. The main toxic effects of dietary exposure to melamine in rats and mice were calculi formation, inflammatory reactions and hyperplasia in the urinary bladder. Melamine is reported to have an oral LD50 of 3248 mg/kg based on rat data. The reported dermal LD50 is > 1000 mg/kg for rabbits. In a study conducted in 1945, large doses of melamine were given orally to rats, rabbits and dogs with no significant toxic effects observed. Melamine crystalluria has been reported in dogs. Haematuria has been reported in rats.

While melamine and cyanuric acid are of low acute toxicity, evidence from the outbreak of acute renal failure in cats and dogs in 2007, associated with the consumption of contaminated pet food suggests, that when melamine and cyanuric acid are co-ingested renal toxicity results. In the pet food incident, analysis of the food revealed the presence of a number of triazine compounds in the feed including melamine and cyanuric acid. A small study in which cats were fed increasing amounts of melamine and cyanuric acid also reported renal failure and the presence of renal crystals. This was confirmed by Dobson et al (2008) who conducted a rat study that tested ingestion of melamine alone, ammeline or ammelide alone (both analogs of melamine), a mixture of melamine and cyanuric acid and a mixture of all four compounds. Neither ammeline nor ammelide alone produced any renal effects, but the mixtures produced significant renal damage and crystals in nephrons. Analysis confirmed the presence of melamine and cyanuric acid in the kidney. Infrared microspectroscopy on individual crystals from rat and cat (from the pet food outbreak) kidneys confirmed that they were melaminecyanuric acid co-crystals.

Melamine also causes some chronic toxicity. Ingestion of melamine leads to reproductive damage and bladder or kidney stones, which can lead to bladder cancer. A study in 1953 reported that dogs fed with 3% melamine for a year had the following changes in their urine: (1) reduced specific gravity, (2) increased output, (3) melamine crystalluria, and (4) protein and occult blood. A survey commissioned by the American Association of Veterinary Laboratory Diagnosticians suggested that crystals formed in the kidneys melamine combined with cyanuric acid do not dissolve easily. They go away slowly, if at all, so there is, the potential for chronic toxicity.

Melamine cyanurate has very low solubility and it is hypothesised that this leads to the formation of melamine cyanurate crystals in the kidney. It is assumed that melamine and cyanuric acid are absorbed in the GI tract, distributed systemically and, for reasons that have not yet been fully determined, precipitate in the renal tubules leading to -progressive tubular blockage and degeneration.

Most of the sub-chronic and chronic feeding studies in animals have failed to show any renal toxicity. In female rats, however, a 13 week feeding study found dose-related calcareous deposits in the proximal tubules and following a two-year feeding study chronic inflammation of the kidney was seen. In rats and dogs,, high doses of melamine had diuretic properties, but did not produce renal toxicity.

Induction of carcinomas of the urinary bladder occurred in male rats fed with diets containing melamine at 4500 ppm (equivalent to 225 mg/kg bw per day) for 103 weeks, but not in female rats or in male or female mice. Tumours are significantly associated with the development of bladder calculi and are related to the administration of high doses.

In 2007, a pet food recall was initiated by Menu Foods and other pet food manufacturers who had found their products had been contaminated and caused serious illnesses or deaths in some of the animals that had eaten them. In March 2007, the US Food and Drug Administration reported finding white granular melamine in the pet food, in samples of white granular wheat gluten imported from a single source in China.

In April, 2007, The New York Times reported that the addition of "melamine scrap" into fish and livestock feed to give the false appearance of a higher level of protein was an open secret in many parts of mainland China. Four days later, the New York Times reported that, despite the widely reported ban on melamine use in vegetable proteins in mainland China, at least some chemical manufacturers continued to report selling it for use in animal feed and in products for human consumption. Another recall incident in 2007 involved melamine which had been purposely added as a binder to fish and livestock feed manufactured in the United States. This was traced to suppliers in Ohio and Colorado.

In September, 2008, several companies were implicated in a scandal involving milk and infant formula which had been adulterated with melamine, leading to kidney stones and other renal failure, especially among young children. By September 22, nearly 53,000 people had become ill, with more than 12,800 hospitalizations and four infant deaths.

Melamine may have been added to deceive government protein content tests after water was added to fraudulently dilute the milk. Because of high nitrogen content (66% by mass versus approximately 10-12% for typical protein) of melamine it can cause the protein content of food to appear higher than the true value. Officials in China have found out that about 20 percent of the dairy companies tested in China sell products tainted with melamine.

The Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA) provides a test method for analysing cyromazine and melamine in animal tissues in its Chemistry Laboratory Guidebook which contains test methods used by FSIS Laboratories to support the Agency’s inspection program, ensuring that meat, poultry, dairy and egg products are safe, wholesome and accurately labeled. In 1999, in a proposed rule published in the Federal Register regarding cyromazine residue, the United States Environmental Protection Agency (EPA) proposed removing melamine, a metabolite of cyromazine from the tolerance expression since it is no longer considered a residue of concern. Melamine, classified a controlled substance in China, has been illegally used in the high profile 2008 baby milk scandal case which led to the death of at least four infants.

Melamine at ppm level (1 part per million) in food and beverage has been reported due to migration from melamine-containing resins which is often used in food packaging and tableware. Small amounts of melamine have also been reported in foodstuff as a metabolite product of cyromazine, an insecticide used crops.

On October 3, 2008, the U.S. Food and Drug Administration said that up to 2.5 parts per million of melamine was safe for adults, but declined to set a standard for children. However, anything less than zero tolerance would not protect consumers.

Until the 2007 pet food recalls, melamine had not routinely been monitored in food, except in the context of plastic safety or insecticide residue. This could be due to the previously assumed low toxicity of melamine, and the relatively expensive methods of detection.

In October, 2008, the U.S. FDA issued new methods for the analysis of melamine and cyanuric acid in infant formulations in the Laboratory Information Bulletin No 4421. Similar recommendations have been issued by other authorities, like the Japanese Ministry of Health, Labour and Welfare, both based on Liquid Chromatography-Mass Spectrometry/Mass Spectro-metry (LC MS/MS) detection after Hydrophilic Interaction LIquid Chromatography (HILIC) separation.